tbuckley/cabot-search huggingface dataset:
Physical performance limitations and participation restrictions among cancer survivors: A population-based study from NHANES data 2015-2018.
Authors: Samantha A. Myers, Emily R Finch, Kirsten K. Ness, Kristin L. Campbell
Journal: Journal of Clinical Oncology (2022)

12096 Background: Anti-cancer therapies have improved survival outcomes in cancer survivors; however, therapy-related toxicities may impact organ structure and function and interfere with physical performance and participation in life roles. This analysis aimed to estimate the prevalence of physical performance limitations (PL) and participation restrictions (PR) among recent (&lt; 5 years since diagnosis), and long-term (≥ 5 years) cancer survivors. Methods: Data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed using multivariable logistic regression, accounting for age, sex, race, and income, and incorporating survey sampling methodology. Odds ratios compared proportions of PL and PR among 663 (weighted population estimate 14,319,219) recent and 341 (weighted population estimate 7,261,088) long-term survivors, and 10,284 (weighted population estimate 215,042,155) persons with no reported cancer history. Two-sided two sample z-tests were used to compare proportions to a previous publication of data from 1999-2002 NHANES data. Results: Physical performance limitations were 1.5-1.7 times (63% vs 29%) and PR 1.5-1.6 times (38% vs 18%) more prevalent in cancer survivors than in those with no cancer history. Long-term cancer diagnosis was associated with increased prevalence of PL and PR, particularly in survivors aged 20-39 years. Proportions increased by 7% for PL and by 10% for PR compared to 1999-2002 values (p-values &lt;0.001). Conclusions: Over 60% of cancer survivors reported PL and nearly 40% reported PR. Despite an interim increase in evidence of the benefits of exercise to manage therapy-related toxicities, these values are a significant increase when compared to 1999-2002 NHANES data. Targeted education for providers and exercise interventions aimed to improve physical function and performance in early cancer survivors should be considered to address the physical sequelae from anti-cancer therapies. [Table: see text]
EPEN-22. Molecularly aggressive ependymomas treated with Image guided pencil beam proton therapy: consecutive patient Indian experience
Authors: Rishan Thimma Sudarsan, Srinivas Chilukuri, M P Noufal, R Adhithyan, Ramya Uppuluri, Pankaj Kumar Panda, Sushma Patil, Dayananda Sharma, V R Roopesh Kumar, Rakesh Jalali
Journal: Neuro-Oncology (2022)

Abstract AIM: To assess the toxicities and early clinical outcomes in patients of primary and recurrent ependymomas treated with image guided pencil beam scanning proton beam therapy (PBS-PBT). MATERIALS AND METHODS: Between January 2019- December 2021, we analyzed consecutive patients of ependymomas treated with image guided PBS-PBT. They were also analyzed molecularly, and all recurrent/re-irradiated patients were considered for craniospinal irradiation (CSI). Acute toxicities were assessed based on NCI CTC v5.0, local control and radiological response by 3-monthly MRI post therapy. RESULTS: Seventeen consecutive patients with ependymoma (13 Grade III and 4 Grade II) (median age-9 years) were analyzed. 9 patients were primary, 7 were treated at first recurrence and 1 at second recurrence. Majority had posterior fossa (PF) tumors (12) followed by supratentorial (ST) (3) and spine (2). Among PF ependymomas, 10 had global loss of H3K27me3, whereas amongst ST, 1 had YAP1 fusion, 1 had L1CAM positivity and other, negative L1CAM and p65/RELA on immunohistochemistry. Gross/near-total resection was achieved in 87% patients. Primary ependymomas were treated with focal radiotherapy; and among recurrent cases, 7 received CSI followed by primary site boost to a total median dose of 55CGE (50.2-55.8CGE). Grade 2 dermatitis, grade 2 and 3 hematological toxicities (CSI) were noted in 3,2 and 2 patients respectively. Grade 2 fatigue noted in 53% of all and 71% receiving CSI. With a median follow-up of 10 months (2-24 months), local control (LC) and disease-free survival (DFS) was 87.5% (primary-100%, recurrent-75%) and overall survival (OS) was 94% (primary-100%, recurrent-88%). CONCLUSION: Our experience of treating patients of ependymoma with complete resection followed by PBS-PBT including CSI is encouraging with low acute toxicities. Recurrent/molecularly aggressive cases may be considered for CSI. Keywords: PT, proton beam therapy, ependymomas, primary and recurrent
RONC-05. Peri-transplant Radiation Therapy for Young Children Treated with High-Dose Chemotherapy for Primary Brain Tumors
Authors: Sarah Milgrom, Jane Koo, Nicholas Foreman, Arthur Liu, Kristen Campbell, Kathleen Dorris, Adam Green, Nathan Dahl, Andrew Donson, Rajeev Vibhakar, Jean Mulcahy-Levy
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: The role of peri-transplant radiation therapy (RT) in young children with primary brain tumors is unclear. We characterized our institutional practice patterns and patient outcomes. MATERIALS AND METHODS: The cohort included all patients treated with high-dose chemotherapy for primary brain tumors at our institution from 2011-2017. Rates of local control (LC), progression-free survival (PFS), overall survival (OS), and radiation-associated injury were assessed. RESULTS: Of 37 eligible patients, 29 (78%) received peri-transplant RT at a median age of 4 years. Patients treated with RT were more likely to have metastatic (p=0.0121) and incompletely resected (p=0.056) disease, and to have high-risk histologies including atypical teratoid rhabdoid tumor, nongerminomatous germ cell tumor, pineoblastoma, primitive neuro-ectodermal tumor, glioneuronal tumor and group 3 medulloblastoma. Of those treated with RT, 13 (45%) received craniospinal irradiation (CSI) and 16 (55%) received focal RT. The median CSI dose was 23.4 Gy (IQR: 18-36; boost median 54 Gy [IQR: 53.7-55.8]) and focal RT dose was 50.4 Gy (IQR: 50.4-54.5). Compared to the focal RT group, patients treated with CSI were older (p=0.0499) and more likely to have metastatic disease (p=0.0004). For the complete cohort, at a median follow-up of 3.8 years, the 2-year rate of LC was 82% (95% CI: 70-96%), PFS was 63% (95% CI: 49-81%), and OS was 65% (95% CI: 51-82%). These rates did not differ significantly between patients treated with and without peri-transplant RT. Two cases of fatal myelopathy were observed after spinal cord doses within the highest tertile (41.4 CGE and 36 Gy); both cases occurred in patients who received RT before high-dose chemotherapy. CONCLUSION: Peri-transplant RT was used for high-risk disease. Oncologic outcomes after RT were encouraging. However, 2 cases of grade 5 myelopathy were observed. If used cautiously, RT may contribute to durable remission in patients at high risk of relapse.
A systematic review on smoldering multiple myeloma: Whether treatment is beneficial.
Authors: Sanjivani Sathe, Insija Ilyas Selene, Jemin Jose, Biplov Adhikari, Syed Hamza Bin Waqar, Zunairah Shah, Mobeen Zaka Haider, Faiz Anwer
Journal: Journal of Clinical Oncology (2022)

e20029 Background: Smoldering multiple myeloma (SMM) is an asymptomatic proliferative disorder of plasma cells. There are multiple early intervention strategies investigated in the last ten years, including single v/s combination therapy, which can either delay progression or be used as an aggressive therapy to cure SMM. This study aims to summarize the reported outcomes of interventions in SMM within the past decade. Methods: We performed a literature search following PRISMA guidelines and used the following bibliographic databases: PUBMED, EMBASE, Cochrane Library, Web of Science, and clinical trials.gov. A total of 1474 articles were found from the above-mentioned databases and a total of seven articles were included in the final analysis. Results: Seven clinical trials were finalized, which included 599 patients, gender was specified in five studies and constituted 51 percent female patients, and the remaining were males. The median age of patients ranges from 61 (21-89) years. In progression evaluation, four studies, 440 patients were considered. However, significant heterogeneity existed with treatments and the survival analysis hence cumulative PFS was not obtained. PFS greater than 90% was obtained in two studies; 95.5% was obtained with Carfilzomib (K), lenalidomide (R), and dexamethasone(d) regimen after a follow-up period of 31.9 months. PFS of 91% was obtained with Lenalidomide alone for a follow-up of 35 months. Three studies, including 200 patients, were evaluated for response rate. MRD negative CR of 70.4% was obtained with the use of the KRd regimen. Overall response (ORR) of intense and intermediate use of Daratumumab showed a rate of 56.7% and 53.1%, while the complete response in the respective arms was 4.9% and 9.8%. CR, stringent CR of 17.4% and 4.3% was obtained with the use of Isatuximab with Lenalidomide. Conclusions: No definite conclusion can be made due to variability in the data. However, based on the data analyzed from the seven clinical trials, we advocate for early therapeutic intervention in high-risk SMM patients. There are multiple ongoing clinical trials to answer whether we should treat SMM or not.[Table: see text]
Clonal evolution and TCR specificity of the human T <sub>FH</sub> cell response to <i>Plasmodium falciparum</i> CSP
Authors: Ilka Wahl, Anna S. Obraztsova, Julia Puchan, Rebecca Hundsdorfer, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. Hoffman, Peter G. Kremsner, Benjamin Mordmüller, Hedda Wardemann
Journal: Science Immunology (2022)

T follicular helper (T FH ) cells play a crucial role in the development of long-lived, high-quality B cell responses after infection and vaccination. However, little is known about how antigen-specific T FH cells clonally evolve in response to complex pathogens and what guides the targeting of different epitopes. Here, we assessed the cell phenotype, clonal dynamics, and T cell receptor (TCR) specificity of human circulating T FH (cT FH ) cells during successive malaria immunizations with radiation-attenuated Plasmodium falciparum ( Pf ) sporozoites. Repeated parasite exposures induced a dynamic, polyclonal cT FH response with high frequency of cells specific to a small number of epitopes in Pf circumsporozoite protein (PfCSP), the primary sporozoite surface protein and well-defined vaccine target. Human leukocyte antigen (HLA) restrictions and differences in TCR generation probability were associated with differences in the epitope targeting frequency and indicated the potential of amino acids 311 to 333 in the Th2R/T* region as a T cell supertope. But most of vaccine-induced anti–amino acid 311 to 333 TCRs, including convergent TCRs with high sequence similarity, failed to tolerate natural polymorphisms in their target peptide sequence, thus demonstrating that the T FH cell response was limited to the vaccine strain. These data suggest that the high parasite diversity in endemic areas will limit boosting of the vaccine-induced T FH cell response by natural infections. Our findings may guide the further design of PfCSP-based malaria vaccines able to induce potent T helper cell responses for broad, long-lasting antibody responses.
“The Oizys Study”: Prevalence and impact of scan-related anxiety on QoL among Greek cancer patients and their caregivers.
Authors: Filippos Koinis, Vasiliki Leontopoulou, Evangelia Chantzara, Athanasios Kotsakis
Journal: Journal of Clinical Oncology (2022)

e24118 Background: Diagnostic imaging may be a major source of distress in patients with advanced cancer, a condition known as “scanxiety”. Scanxiety represents a complex array of negative and stressful emotions linked with cancer scans, and the uncertainties and fears that may accompany them. We aimed to evaluate the prevalence and characterize risk factors for scanxiety among cancer patients and their caregivers and evaluate the impact of scanxiety on quality of life (QoL), during the COVID-era. Methods: We conducted a cross-sectional survey study of metastatic cancer patients treated at the University Hospital of Larisa and their caregivers. Eligible patients met the following inclusion criteria: age &gt; 18 years old, ability to speak and write fluently in Greek, having had at least one imaging study during the period of the study ( seven days before the survey), approval of the patient’s oncologist to approach the patient. Patients/caregivers with pre-existing (prior to cancer diagnosis anxiety disorder) were excluded from the study. After completion of the informed consent process, patients/caregivers completed all survey items. We used a modified version of the Greek version of the Impact of Event Scale-Revised (IES-R-Gr) to specifically assess distress associated with scans, and QoL was measured using the EORTC QLQ-C30 questionnaire. Results: 218 patients with metastatic cancer and their caregivers were included in the study. Patient's mean age was 66 years (range 35-88). The majority were men (61%) and were diagnosed with Non-Small-Cell Lung Cancer. 71% had an IES-R-Gr score that was suggestive of scanxiety. Their symptoms were more severe symptoms while waiting for the results. Patients with a recent diagnosis (&lt; 6 months) had higher levels. Interestingly, 16% of the patients had postponed a check-up due to scanxiety, while 77% reported that stress does not decrease over time. The majority of caregivers (81%) reported scanxiety, without a strong correlation with the score of the respective patients. Unlike patients, the majority of caregivers reported an increase in stress during the COVID-19 period. The presence of scanxiety was associated with decreased QoL in patients (p = 0.004). Conclusions: Scanxiety is a common problem among patients with metastatic cancer and is associated with impaired QoL. To our knowledge this is the first study implying that caregivers also experience scanxiety and may be a persistent problem.
Therapeutic effects and clinical outcomes of immune checkpoint inhibitors on bone metastases in lung cancer.
Authors: Yohei Asano, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Hirotaka Yonezawa, Sei Morinaga, Shiro Saito, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2022)

e21118 Background: In recent years, advanced lung cancer patients who received immune checkpoint inhibitors (ICIs) reportedly had a more prolonged overall survival (OS) than those treated with conventional anticancer drugs. However, the therapeutic effect of ICIs on bone metastases remains unclear. The purpose of this study was to investigate the therapeutic effects of ICIs on advanced lung cancer with bone metastasis. Methods: This retrospective study included 58 lung cancer patients (42 men and 16 women; mean age, 66.2±7.8 years) who had been diagnosed with bone metastasis before the initiation of ICI treatment between 2016 and 2019, and the mean follow-up period was 23.2 months. The clinical data such as content of chemotherapy including the bone-modifying agent (BMA), skeletal-related events (SREs), and immune-related adverse events (irAEs) were investigated. The therapeutic effects of ICIs on the primary lung lesions and bone metastases were evaluated by the response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and MD Anderson criteria, respectively. To assess the influence of ICI treatment on prognosis, OS from the diagnosis of bone metastases was compared to the prognostic prediction of Katagiri's score. Results: The most used ICI was pembrolizumab in 27 cases (46.6%). BMA was used in 38 cases (65.6%), and denosumab was used in 31 cases (81.6%). SREs and irAEs were observed in three cases (5.2%) and 13 cases (22.4%), respectively. In the primary lung lesions, the response rate (RR) and disease control rate (DCR) of ICIs were 14.3% and 38.1%, respectively, including one case in CR and 5 cases in PR. In the bone metastatic lesions, the RR and DCR were 38.6% and 75.0%, respectively, including 3 cases in CR and 14 cases in PR. In 17 cases that ICIs responded to bone metastases, nine cases were treated with pembrolizumab (52.9%), and all cases whose evaluations were CR had been treated with concomitant therapy of pembrolizumab and denosumab. The median survival time was 28.1 months and the 2-year OS rate was 51.7%. The 6-, 12-, and 24-month OS rates in this study were more favorable than the prognostic prediction of the Katagiri's score. Conclusions: ICI treatment showed favorable responses to bone metastases in NSCLC and better prognoses than conventional predictive prognosis. Particularly, pembrolizumab may be the most effective, and the therapeutic effect was enhanced by the concomitant use of denosumab.[Table: see text]
HGG-47. Comparative analysis of the Histone H3 mutant protein interactome landscape in paediatric high-grade gliomas
Authors: William Porter, Joshua Sulman, Katie Foot, Ruman Rahman, Richard Grundy, Robert Layfield, Farhana Haque
Journal: Neuro-Oncology (2022)

Abstract There have been no significant improvements in the treatments for childhood and adolescent High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), which have a very poor prognosis. These cancers harbour mutations affecting histone 3 (H3) proteins, 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. Several studies have highlighted the epigenetic changes associated with these mutations, however their precise role in tumourigenesis is still unknown. We hypothesize that H3 mutations promote an aberrant interaction landscape and analysis of these interactome will highlight important pathophysiological consequences in these tumours. Two different affinity chromatographic proteomic analyses were performed using different recombinant H3 wild type (WT) and H3 mutant histone proteins (K27M, G34R and G34V) to purify their binding partners, from cell extracts of control and pHGG/DIPG patients cell lines. The purified samples were then subjected to Liquid Chromatography-Mass Spectrometry (LC-MS) to identify their co-bound partners. The results have isolated unique and common differential interaction partners of the H3 mutants and with cellular proteins in comparison to H3 WT protein, in the pHGG tumour cells. The role these altered protein interactions are being investigating in tumour initiation, progression and/or maintenance of H3 mutated pHGG/DIPG, with the aim to manipulate their function as alternate therapeutic intervention. Results of these analyses/experiments will be presented.
Aromatase inhibitors for breast cancer therapy: Analysis of real-world FAERS data.
Authors: Dawood Findakly, Runhua Shi, Gary Von Burton, Samip R. Master
Journal: Journal of Clinical Oncology (2022)

1051 Background: Aromatase inhibitors (AIs) are extremely effective adjuvant treatment in postmenopausal women with hormone receptor-positive breast cancer (HRPBC). We utilized the Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate the musculoskeletal (MSK), fractures, and ischemic heart disease (IHD) adverse events (AEs) caused by AIs. Methods: We conducted a retrospective FAERS public database review to assess the MSK, fracture, and IHD AEs for the three AIs (anastrozole, letrozole, and exemestane) from 2001 through 2021. Chi-square was used to compare categorical variables. Results: A total of 31,683 AEs reports were identified, out of which, 15,140 (47.8%) were MSK, 13,311 (42.0%) were fracture, and 3,232 (10.2%) were IHD. The differences in AEs distributions among the three drug classes were statistically significant for MSK and fracture AEs (P &lt; 0.001) but not reached statistical significance for IHD AEs (P = 0.140). MSK AEs were mostly reported with anastrozole, followed by exemestane, and letrozole in 35.23%, 33.97%, and 32.06%, respectively (P &lt; 0.001). Compared to older individuals, younger adults (≤65 years) had higher rates of MSK AEs—mostly with anastrozole (38.43%, P &lt; 0.001), followed by exemestane (36.37%, P = 0.006) and letrozole (34.28%, P &lt; 0.001). Fracture AEs were mostly reported, in descending order, with letrozole, exemestane, and anastrozole in 12.07%, 11.41%, and 9.34% respectively (P &lt; 0.001). Older adults (&gt; 65 years) had higher rates of fracture AEs with letrozole (16.77%, P &lt; 0.001) and anastrozole (10.37%, P &lt; 0.001), while unable to demonstrate statistical significance with exemestane (13.48%, P = 0.108). Among older adults (&gt; 65 years), IHD AEs were significantly reported with anastrozole (21.56%, P &lt; 0.001) and exemestane (14.18%, P = 0.016) but no statistical significance reached for letrozole (14.12%, P = 0.528). Conclusions: The findings in this study highlight trends for selected AEs with various AI regimens, provide further insights, and help guide therapeutic decisions for patients with HRPBC.
Effectiveness of weight management interventions for adults delivered in primary care: systematic review and meta-analysis of randomised controlled trials
Authors: Claire D Madigan, Henrietta E Graham, Elizabeth Sturgiss, Victoria E Kettle, Kajal Gokal, Greg Biddle, Gemma M J Taylor, Amanda J Daley
Journal: BMJ (2022)

Abstract Objective To examine the effectiveness of behavioural weight management interventions for adults with obesity delivered in primary care. Design Systematic review and meta-analysis of randomised controlled trials. Eligibility criteria for selection of studies Randomised controlled trials of behavioural weight management interventions for adults with a body mass index ≥25 delivered in primary care compared with no treatment, attention control, or minimal intervention and weight change at ≥12 months follow-up. Data sources Trials from a previous systematic review were extracted and the search completed using the Cochrane Central Register of Controlled Trials, Medline, PubMed, and PsychINFO from 1 January 2018 to 19 August 2021. Data extraction and synthesis Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Meta-analyses were conducted with random effects models, and a pooled mean difference for both weight (kg) and waist circumference (cm) were calculated. Main outcome measures Primary outcome was weight change from baseline to 12 months. Secondary outcome was weight change from baseline to ≥24 months. Change in waist circumference was assessed at 12 months. Results 34 trials were included: 14 were additional, from a previous review. 27 trials (n=8000) were included in the primary outcome of weight change at 12 month follow-up. The mean difference between the intervention and comparator groups at 12 months was −2.3 kg (95% confidence interval −3.0 to −1.6 kg, I 2 =88%, P&lt;0.001), favouring the intervention group. At ≥24 months (13 trials, n=5011) the mean difference in weight change was −1.8 kg (−2.8 to −0.8 kg, I 2 =88%, P&lt;0.001) favouring the intervention. The mean difference in waist circumference (18 trials, n=5288) was −2.5 cm (−3.2 to −1.8 cm, I 2 =69%, P&lt;0.001) in favour of the intervention at 12 months. Conclusions Behavioural weight management interventions for adults with obesity delivered in primary care are effective for weight loss and could be offered to members of the public. Systematic review registration PROSPERO CRD42021275529.